A furin cleavage site was discovered in the S protein of the 2019 novel coronavirus.
A furin cleavage site was discovered in the S protein of the 2019 novel coronavirus.
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DOI：
10.12113/202002001
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发表时间：
2020-01-01
期刊：
影响因子：
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通讯作者：
Ruan, J. S.
中科院分区：
文献类型：
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作者：
Li, Xin;Duan, Guang-you;Ruan, J. S.
2019年新型冠状病毒（2019-nCoV）导致武汉（中国城市）的肺炎疫情。在我们之前的研究中，分析结果显示，2019-nCoV和SARS冠状病毒都属于β冠状病毒亚组B（BB冠状病毒），但差异较大，这与两种相关疾病临床症状的差异相吻合。最重要的发现是Nankai CDS的替代翻译可以产生超过17个推测的蛋白质，这些蛋白质可能与宿主适应有关。利用17种蛋白质对13种病毒进行基因分型，结果表明BB冠状病毒具有较高的突变率和多样性。本研究首次（2020年1月21日）报告了β冠状病毒刺突（S）蛋白的一个非常重要的突变。通过这种突变，2019-nCoV在其S蛋白中获得了弗林蛋白酶的切割位点，这在大多数其他β冠状病毒（例如SARS冠状病毒）的S蛋白中不存在。这个切割位点可能会提高病毒感染细胞的效率，使得2019-nCoV具有比SARS冠状病毒明显更强的传播性。2019-nCoV的感染机制可能会改变，与MHV，HIV，埃博拉病毒（EBoV）和一些禽流感病毒的感染机制更相似，而不是大多数其他β冠状病毒（e. G. SARS冠状病毒）。此外，我们意外地发现，一些禽流感病毒通过与2019-nCoV类似的突变获得了弗林蛋白酶的切割位点。因此，天然突变可导致短插入以形成弗林蛋白酶的切割位点。2019-nCoV中弗林蛋白酶的切割位点含有编码两个精氨酸（R）残基的“CGGCGG”序列。然而，“CGG”是人类的罕见密码子。因此，我们得出结论，这两个密码子在2019-nCoV样β冠状病毒传播到人类之前就存在于其中，并且中间宿主是具有较高相对频率的“CGG”使用的哺乳动物。我们提供了哺乳动物中“CGG”使用的相对频率表，以帮助识别2019-nCoV的中间宿主。未来对这种突变的研究将有助于揭示2019-nCoV更强的传播性，并为但不限于2019-nCoV的疫苗开发和药物设计奠定基础。
The 2019 novel Coronavirus (2019-nCoV) has caused the pneumonia outbreak in Wuhan (a city of China). In our previous study, the analytical results showed that both 2019-nCoV and SARS coronavirus belong to Betacoronavirus subgroup B (BB coronavirus), but have large differences, which are consistent with the differences in the clinical symptoms of two related diseases. The most important finding was that the alternative translation of Nankai CDS could produce more than 17 putative proteins, which may be responsible for the host adaption. The genotyping of 13 viruses using the 17 putative proteins revealed the high mutation rate and diversity of BB coronavirus. The present study for the first time (on January 21st, 2020) reported a very important mutation in the Spike (S) proteins of Betacoronavirus. By this mutation, 2019-nCoV acquired a cleavage site for furin enzyme in its S protein, which is not present in the S proteins of most other Betacoronavirus (e.g. SARS coronavirus). This cleavage site may increase the efficiency of virus infection into cells, making 2019-nCoV has significantly stronger transmissibility than SARS coronavirus. The infection mechanism of 2019-nCoV may be changed to being more similar to those of MHV, HIV, Ebola virus (EBoV) and some avian influenza viruses, other than those of most other Betacoronavirus (e. g. SARS coronavirus). In addition, we unexpectedly found that some avian influenza viruses acquired a cleavage site for furin enzyme by the similar mutation as 2019-nCoV. Therefore, the natural mutation can result in a short insertion to form a cleavage site for furin enzyme. The cleavage site for furin enzyme in 2019-nCoV contains the "CGGCGG" sequence encoding two arginine (R) residues. "CGG", however, is a rare codon for human. So we concluded that these two codons were present in the 2019-nCoV -like Betacoronavirus before they transmitted into human and the intermediate host (s) are mammals with a high relative frequency of "CGG" usage. We provide a relative frequency table of " CGG" usage in mammals to help identify the intermediate hosts of 2019-nCoV. Future studies of this mutation will help to reveal the stronger transmissibility of 2019-nCoV and lay foundations for vaccine development and drug design of, but not limited to 2019-nCoV.